THE 46-KDA MANNOSE 6-PHOSPHATE RECEPTOR CONTAINS MULTIPLE BINDING-SITES FOR CLATHRIN ADAPTERS

The two known mannose 6-phosphate receptors (MPR46 and MPR300) both me diate the transport of Man-6-P-containing lysosomal proteins to lysoso mes. However, the MPRs cannot be detected in lysosomes, instead they r ecycle between the plasma membrane and endosomes and between endosomes and the trans-Golgi network. Both, endocytosis from the plasma membra ne and budding of transport vesicles from the trans-Golgi network invo lves the interaction of the receptor with the clathrin-coated vesicles -associated protein complexes AP1 and AP2. We have analyzed this inter action between the Golgi-restricted AP1 complex and the plasma membran e-restricted AP2 complex with the MPR46 tail in vitro by using a biose nsor. AP1 and AP2 both bind to and dissociate from the MPR46 tail with similar kinetics, Using synthetic peptides corresponding to different MPR receptor tail regions in inhibition and binding studies, a common high affinity binding site for AP1 and AP2 and two separate high affi nity binding sites for AP1 and AP2, respectively, were identified.